Electric Fields in Liquid Water Irradiated with Protons at Ultrahigh Dose Rates.

We study the effects of irradiating water with 3 MeV protons at high doses by observing the motion of charged polystyrene beads outside the proton beam. By single-particle tracking, we measure a radial velocity of the order of microns per second. Combining electrokinetic theory with simulations of the beam-generated reaction products and their outward diffusion, we find that the bead motion is due to electrophoresis in the electric field induced by the mobility contrast of cations and anions. This work sheds light on the perturbation of biological systems by high-dose radiations and paves the way for the manipulation of colloid or macromolecular dispersions by radiation-induced diffusiophoresis.

Development of gas jet targets for laser-plasma experiments at near-critical density.

Computational fluid dynamics simulations are performed to design gas nozzles, associated with a 1000 bars backing pressure system, capable of generating supersonic gas jet targets with densities close to the critical density for 1053 nm laser radiation (1021 cm-3). Such targets should be suitable for laser-driven ion acceleration at a high repetition rate. The simulation results are compared to the density profiles measured by interferometry, and characterization of the gas jet dynamics is performed using strioscopy. Proton beams with maximum energies up to 2 MeV have been produced from diatomic hydrogen gas jet targets in a first experiment.

Levodopa medication improves incidental sequence learning in Parkinson's disease.

Empirical evidence suggests that levodopa medication used to treat the motor symptoms of Parkinson's disease (PD) may either improve, impair or not affect specific cognitive processes. This evidence led to the 'dopamine overdose' hypothesis that levodopa medication impairs performance on cognitive tasks if they recruit fronto-striatal circuits which are not yet dopamine-depleted in early PD and as a result the medication leads to an excess of dopamine. This hypothesis has been supported for various learning tasks including conditional associative learning, reversal learning, classification learning and intentional deterministic sequence learning, on all of which PD patients demonstrated significantly worse performance when tested on relative to off dopamine medication. Incidental sequence learning is impaired in PD, but how such learning is affected by dopaminergic therapy remains undetermined. The aim of the current study was to investigate the effect of dopaminergic medication on incidental sequence learning in PD. We used a probabilistic serial reaction time task (SRTT), a sequence learning paradigm considered to make the sequence less apparent and more likely to be learned incidentally rather than intentionally. We compared learning by the same group of PD patients (n=15) on two separate occasions following oral administration of levodopa medication (on state) and after overnight withdrawal of medication (off state). Our results demonstrate for the first time that levodopa medication enhances incidental learning of a probabilistic sequence on the serial reaction time task in PD. However, neither group significantly differed from performance of a control group without a neurological disease, which indicates the importance of within group comparisons for identifying deficits. Levodopa medication enhanced incidental learning by patients with PD on a probabilistic sequence learning paradigm even though the patients were not aware of the existence of the sequence or their acquired knowledge. The results suggest a role in acquiring incidental motor sequence learning for dorsal striatal areas strongly affected by dopamine depletion in early PD.

Abnormal Sensitivity to Glucagon and Related Peptides in Primary Adrenal Cushing's Syndrome.

Illegitimate G-protein coupled receptors are known to control cortisol secretion in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs) causing Cushing's syndrome. In the present study, we have evaluated the role of glucagon in the regulation of cortisol secretion in 13 patients with BMAH or adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery, immunohistochemical studies showed the presence of glucagon receptor-like immunoreactivity in clusters of spongiocytic cells in adrenal tissues from patients who were sensitive in vivo to glucagon. We also observed an in vitro cortisol response to vasoactive intestinal peptide from an adenoma, which was insensitive to glucagon and pituitary adenylate cyclase-activating peptide. Altogether, our data show that ectopic glucagon receptors are expressed in some adrenal cortisol-producing benign lesions. Our results also indicate that circulating glucagon may influence cortisol release under fasting conditions.

[Usefulness of endoscopic evaluation with fluorescence after endovesical BCG in the management of non-invasive bladder tumors]. / Quelle place pour l'évaluation endoscopique avec fluorescence après traitement d'attaque par instillations endovésicales de BCG.

INTRODUCTION: The objective of this retrospective study was to assess the usefulness of fluorescence during cystoscopy after BCG-therapy in the management of non-invasive bladder tumors. PATIENTS AND METHODS: Fifty-four patients were enrolled: Ta (15 cases), T1 (27 cases) carcinoma in situ (CIS) alone (12 cases) or associated (14 cases). Urine cytology was of high grade and a second look was systematically performed in case of lamina propria infiltration. Initial therapy with 6 intravesical BCG instillations (81 mg) was performed with histologic and endoscopic bladder evaluation 3 months after initial resection using hexylaminolevulinate fluorescence (Hexvix(®) 85 mg). RESULTS: Urine cytology was negative in 27 cases, suspicious in 12 cases and positive in 15 cases. With standard endoscopy under white light, mucosal bladder was normal in 32 cases, the use of fluorescence detected 8 tumour lesions confirmed with histology (CIS). When mucosal bladder was suspect under white light (22 patients), fluorescence was positive in 16 cases with 10 matching histological analysis (CIS and/or residual tumoral lesion). Therefore, despite high false positive rate with persistent mucosal bladder inflammation (38%), fluorescence guided endoscopy has allowed the diagnosis of suspect lesions not detected with white light with negative urine cytology. CONCLUSION: Hexvix(®) fluorescence after intravesical BCG instillations may improve persistent carcinoma in situ detection when performed 3 months after induction treatment. However, a multicenter prospective study will be necessary in future to confirm these preliminary results. LEVEL OF EVIDENCE: 5.

[Penile gangrene: a rare complication of systemic calciphylaxis, to be screened]. / La gangrène de la verge: une rare complication de la calciphylaxie systémique, à dépister.

Gangrene of the penis is a rare and serious complication of end stage renal disease, being an expression of systemic calciphylaxis. We report the case of a 58-year-old patient with chronic renal failure and diabetes, who presented with a necrosis of the gland. MRI defined the limits of necrosis. The treatment consisted in partial amputation of the penis. Histological examination found a calciphylaxis.

Response functions of imaging plates to photons, electrons and 4He particles.

Imaging plates from Fuji (BAS-SR, MS, and TR types) are phosphor films routinely used in ultra high intensity laser experiments. However, few data are available on the absolute IP response functions to ionizing particles. We have previously measured and modeled the IP response functions to protons. We focus here on the determination of the responses to photons, electrons, and (4)He particles. The response functions are obtained on an energy range going from a few tens of keV to a few tens of MeV and are compared to available data. The IP sensitivities to the different ionizing particles demonstrate a quenching effect depending on the particle stopping power.

Response functions of Fuji imaging plates to monoenergetic protons in the energy range 0.6-3.2 MeV.

We have measured the responses of Fuji MS, SR, and TR imaging plates (IPs) to protons with energies ranging from 0.6 to 3.2 MeV. Monoenergetic protons were produced with the 3.5 MV AIFIRA (Applications Interdisciplinaires de Faisceaux d'Ions en Région Aquitaine) accelerator at the Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG). The IPs were irradiated with protons backscattered off a tantalum target. We present the photo-stimulated luminescence response of the IPs together with the fading measurements for these IPs. A method is applied to allow correction of fading effects for variable proton irradiation duration. Using the IP fading corrections, a model of the IP response function to protons was developed. The model enables extrapolation of the IP response to protons up to proton energies of 10 MeV. Our work is finally compared to previous works conducted on Fuji TR IP response to protons.

[Preliminary study of p53 and FGFR3 gene mutations in the urine for bladder tumors]. / Étude préliminaire des mutations des gènes p53 et FGFR3 sur le culot urinaire des tumeurs de la vessie.

INTRODUCTION: Two major pathways are described in bladder carcinogenesis: one for invasive or high grade tumors characterized by alteration of the p53 tumor suppressor gene and the other for non-invasive tumors or low grade involving mutations FGFR3. The objective of our study was to validate the research in the urine of mutations in these two genes in patients with a bladder tumor. PATIENTS AND METHODS: In our preliminary study, we investigated 36 patients the FGFR3 and p53 mutations in tumors and urine collected during endoscopic resection. The p53 mutations were sought in FASAY, which allows a functional analysis of the protein P53. The FGFR3 mutations were sought in SNaPshot that searches the eight most frequent mutation points of this gene. RESULTS: For 24 patients (66% of cases), we found at least one of the two mutations in the tumor. This mutation was present in the urine in 15 patients (sensitivity=62.5%). In only one patient, we found a mutation in the urinary sediment that did not exist in the tumor (specificity=91.7%). CONCLUSION: The search for mutations of p53 and FGFR3 in the urine was a simple and non-invasive assay, which seems superior to urinary cytology for the detection of bladder tumors, raising hopes of an interest in this bio-assay for surveillance of bladder tumors and screening risk populations.

NATALIE: a 32 detector integrated acquisition system to characterize laser produced energetic particles with nuclear techniques.

We present a stand-alone system to characterize the high-energy particles emitted in the interaction of ultrahigh intensity laser pulses with matter. According to the laser and target characteristics, electrons or protons are produced with energies higher than a few mega electron volts. Selected material samples can, therefore, be activated via nuclear reactions. A multidetector, named NATALIE, has been developed to count the ß(+) activity of these irradiated samples. The coincidence technique used, designed in an integrated system, results in very low background in the data, which is required for low activity measurements. It, therefore, allows a good precision on the nuclear activation yields of the produced radionuclides. The system allows high counting rates and online correction of the dead time. It also provides, online, a quick control of the experiment. Geant4 simulations are used at different steps of the data analysis to deduce, from the measured activities, the energy and angular distributions of the laser-induced particle beams. Two applications are presented to illustrate the characterization of electrons and protons.

[Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients]. / Traitement de la cystite interstitielle par instillation intravésicale d'acide hyaluronique : étude prospective sur 31 patientes.

PURPOSE: We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). PATIENTS AND METHODS: From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). RESULTS: Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. CONCLUSIONS: Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal.

Hot electrons transverse refluxing in ultraintense laser-solid interactions.

We have analyzed the coupling of ultraintense lasers (at ∼2×10{19} W/cm{2}) with solid foils of limited transverse extent (∼10 s of µm) by monitoring the electrons and ions emitted from the target. We observe that reducing the target surface area allows electrons at the target surface to be reflected from the target edges during or shortly after the laser pulse. This transverse refluxing can maintain a hotter, denser and more homogeneous electron sheath around the target for a longer time. Consequently, when transverse refluxing takes places within the acceleration time of associated ions, we observe increased maximum proton energies (up to threefold), increased laser-to-ion conversion efficiency (up to a factor 30), and reduced divergence which bodes well for a number of applications.

[T1 bladder carcinoma: prognostic value of the muscularis mucosae invasion (T1a/T1b). A multicenter study by the French Urological Association (CCAFU)]. / Tumeur urothéliale de vessie T1 : valeur pronostique du franchissement de la muscularis mucosae (T1a/T1b). Etude multicentrique du Comité de cancérologie de l'Association française d'urologie (CCAFU).

OBJECTIVE: The aim of this multicenter study was to determine the prognostic value of the depth of invasion of lamina propria and more specifically the influence of the invasion of the muscularis mucosae on survival parameters in T1 bladder carcinoma. PATIENTS: Six urological centers included patients between 1994 and 2004 who had an initial T1 bladder tumor. All T1 tumors were substaged according to the muscularis mucosae (MM) invasion into T1a (no invasion beyond the MM) and T1b (invasion beyond MM but preserving the muscle). Among the 387 patients included, 269 (69.5%) were found T1a and 118 (30.5%) T1b. Mean follow-up was 45.4 months. T1a and T1b groups were comparable except for tumor grade that was higher in T1b (p<0.001). RESULTS: Survival without recurrence was not significantly different between T1a and T1b groups (p<0.3) but T1a stage was found as an independent factor for survival without progression (RR=0.49; IC 95%=[0.71-0.90]), specific survival (RR=0.33; IC 95%=[0.16-0.67]) and global survival (RR=0.52; IC 95%=[0.32-0.85]). CONCLUSION: This study, the largest on the subject to our knowledge, have shown that muscularis mucosae invasion was a prognostic factor for survival without progression, specific survival, and global survival. We support that routine pathological assessment of the level of MM invasion in patients with stage T1 bladder cancer should be included in the histopathological report.

[Renal angiomyolipoma with inferior vena cava extension]. / Angiomyolipome renal à extension veineuse cave inférieure.

Angiomyolipoma is generally a benign and noninvasive tumor. We report a case of angiomyolipoma with tumor thrombus from the renal vein into the inferior vena cava suggesting a malignant disease.

[Elevation of total PSA after intravesical BCG instillations: granulomatous prostatitis or prostatic adenocarcinoma?]. / Elévation du PSA total après instillations endovesicales de BCG: prostatite granulomateuse ou adénocarcinome prostatique?

OBJECTIVE: The objective of this study was to evaluate the incidence of prostatic carcinoma in patients treated by intravesical BCG-therapy for superficial bladder cancer and presenting granulomatous prostatitis. The authors discuss the problems of interpretation of total PSA and the potential indications for prostatic biopsies in this population. MATERIAL AND METHODS: A retrospective study was performed on the cases of symptomatic granulomatous prostatitis observed among patients treated with intravesical BCG instillations between January 1997 and December 2006. A total of 153 men were treated for high-risk or intermediate-risk superficial bladder cancer according to the usual recommendations. The attenuated Connaught strain of BCG was used at a dose of 81 mg. Induction treatment consisted of six weekly instillations and was followed by maintenance treatment for a period of three years. RESULTS: Six patients developed symptomatic granulomatous prostatitis (4% of cases). On average, this complication occurred after about the 10th intravesical instillation (6-13) of maintenance treatment. The mean total PSA at three months was 8 ng/ml (range: 5-11.6). Ultrasound-guided biopsies were indicated in view of the persistently elevated PSA level and confirmed the tuberculoid granulomatous lesion of the prostate in each case and revealed prostatic adenocarcinoma in two patients. CONCLUSION: Prostatic carcinoma must be systematically excluded by ultrasound-guided biopsies in all patients with clinical granulomatous prostatitis and persistently elevated PSA three months after intravesical BCG instillations.

Fast electron transport and induced heating in solid targets from rear-side interferometry imaging.

Fast adiabatic plasma heating of a thin solid target irradiated by a high intensity laser has been observed by an optical fast interferometry diagnostic. It is driven by the hot electron current induced by the laser plasma interaction at the front side of the target. Radial and longitudinal temperature profiles are calculated to reproduce the observed rear-side plasma expansion. The main parameters of the suprathermal electrons (number, temperature, and divergence) have been deduced from these observations.

High flux of relativistic electrons produced in femtosecond laser-thin foil target interactions: characterization with nuclear techniques.

We present a protocol to characterize the high energy electron beam emitted in the interaction of an ultraintense laser with matter at intensities higher than 10(19) W cm(-2). The electron energies and angular distributions are determined as well as the total number of electrons produced above a 10 MeV threshold. This protocol is based on measurements with an electron spectrometer and nuclear activation techniques, combined with Monte Carlo simulations based on the GEANT3 code. The method is detailed and exemplified with data obtained with polypropylene and copper thin solid targets at a laser intensity of 2x10(19) W cm(-2). Special care is taken of the different sources of uncertainties. In particular, the reproducibility of the laser shots is considered.

Direct evidence of strongly inhomogeneous energy deposition in target heating with laser-produced ion beams.

We report on strong nonuniformities in target heating with intense, laser-produced proton beams. The observed inhomogeneity in energy deposition can strongly perturb equation of state (EOS) measurements with laser-accelerated ions which are planned in several laboratories. Interferometric measurements of the target expansion show different expansion velocities on the front and rear surfaces, indicating a strong difference in local temperature. The nonuniformity indicates at an additional heating mechanism, which seems to originate from electrons in the keV range.